1. Field of the Invention
The present invention relates to a method for preparing an oral formulation containing acid-sensitive drugs, and especially to a method for preparing an oral formulation containing omeprazole having an layer of evenly distributed omeprazole coated on the core.
2. Description of Related Art
The acid-sensitive drugs essentially comprise substituted benzimidazole gastric anti-secretary agent such as omeprazole, lansoprazole, pantoprazole and pharmaceutically acceptable salts thereof. These agents are well-known strong inhibitors for inhibiting gastric acid secretion in mammals. The acid-sensitive drugs have irreversible inhibiting-action against the enzymatic system of H/K ATPase in the human body. In other words, they can inhibit the proton pumps of the gastroparietal cells. However, it is easy for the acid-sensitive drugs to decay in an acidic environment to become non-active ingredients. Therefore, there is a need in the field of the active ingredient manufacturing to overcome the above-mentioned problem.
For example, omeprazole is very unstable in an acidic environment. The half-life of degradation of omeprazole in water solutions at pH-values less than four is shorter than ten minutes. Even at neutral pH-values degradation proceeds rapidly, e.g. at pH=7 the half-life of omeprazole is about 14 hours. Therefore, omeprazole cannot exist in an acidic environment. The stability of omeprazole is also affected by moisture, heat, and organic solvents and to some degree by light. It is reported in some literature that omeprazole possesses acceptable stability in a base environment.
Owing to the stability of omeprazole, omeprazole should not contact gastric acid solution after administering the total formulation containing omeprazole, since the gastric acid solution will lower the activity of the omeprazole. Therefore, the oral formulation containing omeprazole is usually treated with an enteric coating to prevent the omeprazole from direct contact with the gastric acid solution. However, the enteric coating is usually made with acidic chemicals, thus when the oral formulation containing omeprazole is directly treated with the enteric coating, the omeprazole will rapidly decompose due to direct or indirect contact with the acidic ingredient in the enteric coating, such that the oral formulation will be discolored and the activity will be reduced during storage.
One conventional method for preparing an oral formulation containing omeprazole is proposed to overcome the above-mentioned problem. This conventional method consists of stabilizing the omeprazole by putting the omeprazole and a part of the excipients into an ammonia-containing environment instead of utilizing the base core consisting of omeprazole and base chemicals, and then spreading solutions onto the core with an eccentric separator while adding a globing agent from a supply funnel to form pellets containing the active ingredients.
However, the above-mentioned conventional method includes adding a globing agent at any time during preparing the pellets of the oral formulations. Such an addition of globing agent during the preparation of the pellets is very inconvenient in a process for preparing a pellet, and causes variable sizes of pellets resulting in a greater difference in terms of releasing rate of the oral formulation. Therefore, this conventional method is not acceptable to manufactures seeking a preparation method that is operated easily and can produce an homogeneously distributed oral preparation. In addition, the ammonia used in this conventional method also causes a problem of noxious fumes at the preparation site and is not environmentally friendly.
Therefore, there is still a need to provide a method for preparing an oral formulation with acid-sensitive drugs which solves the problem of the difference in pellet size and enhances the consistency of the releasing rate.
The objective of the present invention is to provide a method for preparing an oral formulation containing acid-sensitive drugs having a layer of evenly distributed active ingredient coated on the core.
To achieve the objective, the method in accordance with the present invention comprises:
(a) spreading a solution or a suspension comprising stablizers, solvents and acid-sensitive drugs or its pharmaceutically acceptable salts onto a core made from one or more excipients, and then drying the spread core to make a core with an active ingredient layer;
(b) spreading a solution or suspension comprising adhesives, plasticizer, anti-tackiness and solvents on the active ingredient layer containing the core achieved in (a) and then drying the solution or suspension to form a sub-coating layer over the active ingredient layer; and
(c) spreading a suspension comprising enteric-soluble coating material, plasticizer, anti-tackiness agent and solvents onto the sub-coating layer achieved in (b) and then drying the spread suspension to make an enteric coating layer over the sub-coating layer. With the method in accordance with the present invention, the oral formulation containing acid-sensitive drugs has a layer of evenly distributed active ingredient layer coated on the core without active ingredients.
Other objectives, advantages and novel features of the invention will become more apparent from the following detailed description when taken in conjunction with the accompanying drawings.